Hsa_circ_0004831 downregulation is partially responsible for atorvastatinalleviated human umbilical vein endothelial cell injuries induced by ox-LDL through targeting the miR-182-5p/CXCL12 axis

Abstract

Background The dysfunction and injury of human umbilical vein endothelial cells (HUVECs) are key events of atherosclerosis (AS). Atorvastatin (ATV) has been shown to play a protective role on endothelial cells. However, the associated molecular mechanisms remain not fully illustrated. Methods HUVECs were treated with oxidized low-density lipoprotein (ox-LDL) to mimic the pathological conditions of endothelial cell injury in AS. Cell injuries were assessed according to cell viability, cell apoptosis, cycle progression, oxidative stress and inflammatory responses using CCK-8 assay, flow cytometry assay or commercial kits. The expression of hsa_circ_0004831, miR-182-5p, and C-X-C motif chemokine 12 (CXCL12) mRNA was examined using quantitative real-time PCR (qPCR). The expression of CXCL12 protein was quantitated by western blot. The predicted target relationship between miR-182-5p and hsa_circ_0004831 or CXCL12 was verified by pull-down assay, dual-luciferase reporter assay or RIP assay. Results The expression of hsa_circ_0004831 was upregulated by ox-LDL but downregulated by ATV in HUVECs. ATV promoted cell viability and cell cycle progression but inhibited apoptosis, oxidative stress and inflammation in ox-LDL-treated HUVECs, while the role of ATV was partially reversed by hsa_circ_0004831 overexpression. MiR-182-5p was targeted by hsa_circ_0004831, and hsa_circ_0004831 overexpression-restored apoptosis, oxidative stress and inflammation were blocked by miR-182-5p restoration. Further, CXCL12 was targeted by miR-182-5p, and miR-182-5p inhibition-stimulated apoptosis, oxidative stress and inflammation were lessened by CXCL12 knockdown. Conclusion Hsa_circ_0004831-targeted miR-182-5p/CXCL12 regulatory network is one of the pathways by which ATV protects against ox-LDL-induced endothelial injuries.

Histone Deacetylase 1 Depletion Alleviates Coronary Heart Disease Via the MicroRNA-182–Mediated Transforming Growth Factor β/Smad Signaling Pathway

“…28 Meanwhile, miR-182-5p restoration could partly eradicate the effects of hsa_circ_0004831-induced injuries of human umbilical vein endothelial cells. 29 Previously, the rats suffering from myocardial infarction have been shown to exhibit increased inflammatory factors, blood lipid indexes, TGF-β mRNA and protein expression, and Smad2 phosphorylation, whereas after the TGF-β/Smad pathway blockage, the rats showed notably opposite trend. 30 The interaction between HDAC1 and the TGF-β/Smad pathway has been implicated in renal interstitial fibrosis.…”

Endothelial progenitor cell derived exosomes mediated miR-182-5p delivery accelerate diabetic wound healing via down-regulating PPARG

“…miR-182 has been demonstrated that promote epithelial-mesenchymal transition, invasion and migration and angiogenesis in both breast cancer [39] and HCC [40]. Meanwhile, miR-182-5p could promote the proliferation, migration and angiogenesis of HUVECs [41], indicating the potential role of anti-angiogenic effect in endothelial cells of diabetes. In the current study, we demonstrated that miR-182-5p can positively regulate the diabetic wound healing by targeting PPARG.…”

Upgulation of lncRNA GASL1 inhibits atherosclerosis by regulating miR-106a/LKB1 axis

“…Endothelial cell apoptosis is the main form of endothelial injury and plays an important role in the occurrence and development of AS [ 21 ]. Ox-LDL can lead to endothelial cell injury and promote the occurrence and development of AS [ 22 ]. The results also identified this phenomenon, that is, 50 µg/ml ox-LDL caused the decreased viability of HUVECs.…”